The success of engineered cell or tissue implants is dependent on vascular regeneration to meet adequate metabolic requirements. However, development of a broadly applicable strategy for stable and functional vascularization has remained challenging. We report here highly organized and resilient microvascular meshes fabricated through a controllable anchored self-assembly method. The microvascular meshes are scalable to centimeters, almost free of defects and transferrable to diverse substrates, ready for transplantation. They promote formation of functional blood vessels, with a density as high as ~220 vessels mm-2, in the poorly vascularized subcutaneous space of SCID-Beige mice. We further demonstrate the feasibility of fabricating microvascular meshes from human induced pluripotent stem cell-derived endothelial cells, opening a way to engineer patient-specific microvasculature. As a proof-of-concept for type 1 diabetes treatment, we combine microvascular meshes and subcutaneously transplanted rat islets and achieve correction of chemically induced diabetes in SCID-Beige mice for 3 months.
Based on our results, ultrasound-guided HIFU is safe for the treatment of diffuse adenomyosis, and controlling the ablation zone is crucial to ensure patients' safety.
Objective measurements and their intersection with subjective perceptions demonstrate the influences of inter-generation, season, sex, and living habits on Chinese body skin.
Astrocyte-elevated gene-1 (AEG-1) is implicated in the oncogenesis and angiogenesis of various types of human cancers. However, the biological roles of AEG-1 in cervical carcinoma remain to be further elucidated. In the present study, we demonstrated that the expression of AEG-1 was markedly upregulated in the cervical carcinoma cell lines HeLa, CaSki and SiHa, as well as in 8 paired primary cervical carcinoma tissue (CCT) specimens at both the transcriptional and translational levels when compared with normal cervical epithelial cells (NCECs). Furthermore, immunohistochemical (IHC) analysis demonstrated that 180 of 200 (90%) archived CCT specimens exhibited positive staining for AEG-1, and statistical analysis revealed that the upregulation of AEG-1 was significantly correlated with the clinical staging of the patients (P=0.034), including T (P=0.019), N (P=0.038) and M classification (P=0.018) as well as tumor differentiation (P=0.043). Furthermore, loss‑ and gain‑of‑function results showed that knockdown of AEG-1 expression by specific shRNA not only inhibited SiHa cell proliferation and invasive ability, but also significantly decreased the expression of the angiogenesis-related genes HIF-1α, Tie2, VEGF and TEM1/CD248. Moreover, an increased vascular formation ability was observed in human umbilical vein endothelial cells (HUVECs) co-cultured with conditioned medium both from SiHa cells and NCECs transfected with ectopic AEG-1. In conclusion, these results suggest that elevated expression of AEG-1 plays an important role in the aggressiveness and angiogenesis of cervical carcinoma and that AEG‑1 represents a novel and valuable predictive factor for the prognostic evaluation of cervical carcinoma patients.
Although abundant evidence indicates mutual regulation between the immune and the central nervous systems, how the immune signals are transmitted to the brain is still an unresolved question. In a previous study we found strong expression of proinflammatory cytokine receptors, including interleukin (IL)-1 receptor I and IL-6 receptor alpha in the rat carotid body (CB), a well-known arterial chemoreceptor that senses a variety of chemostimuli in the arterial blood. We demonstrated that IL-1 stimulation increases intracellular calcium ([Ca(2+)](i)) in CB glomus cells, releases ATP, and increases the discharge rate in carotid sinus nerve. To explore the effect of IL-6 on CB, here we examine the effect of IL-6 on [Ca(2+)](i) and catecholamine (CA) secretion in rat CB glomus cells. Calcium imaging showed that extracellular application of IL-6 induced a rise in [Ca(2+)](i) in cultured glomus cells. Amperometry showed that local application of IL-6 evoked CA release from glomus cells. Furthermore, the CA secretory response to IL-6 was blocked by 200 microM Cd(2+), a well-known Ca(2+) channel blocker. Our experiments provide further evidence for the responsiveness of the CB to proinflammatory cytokines and indicate that the CB might play a role in inflammation sensing and transmission of such information to the brain.
The current study was designed to locate the neuronal activation in rat brain following intraperitoneal injection of Staphylococcus enterotoxin B (SEB) and observe the consequence of preliminary subdiaphragmatic vagotomy on SEB-induced brain Fos expression to clarify the role of the vagus nerve in sensation and transmission of abdominal SEB stimulation. The results showed that intraperitoneal SEB (1 mg/kg) induced a robust Fos expression in widespread brain areas. A significant increase of Fos immunoreactive cells were observed in the solitary tract nucleus, locus ceruleus, lateral parabrachial nucleus, ventrolateral part of central gray, medial amygdaloid nucleus, central amygdaloid nucleus, ventromedial part of thalamus, dorsomedial part of thalamus, hypothalamic paraventricular nucleus, lateral habenula, and lateral septum nucleus following SEB challenge. In hypothalamic paraventricular nucleus, in addition to the dense Fos expression in the parvocellular portion, some Fos-positive cells were also observed in the anterior magnocellular nucleus of the complex. Double immunofluorescence studies showed that these Fos-immunoreactive cells were mostly oxytocinergic. The results also showed that subdiaphragmatic vagotomy largely attenuated, but not totally abrogated, the brain Fos expression induced by abdominal administration of SEB. Our data suggest that peripheral SEB stimulation can induce activation of neurons in widespread brain areas and that the vagus plays a crucial role in transmitting the signal of abdominal immune stimulation to the brain.
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